Over the last 10 years laboratory has tested the hypothesis that Paget's disease of bone is similar to a slow virus infection of the central nervous system such as subacute sclerosing panencephalitis caused by a mutant measles virus of the Paramyxoviridae family. We have accumulated electron microscopic and immunohistologic evidence that both measles virus, respiratory syncytial virus and possibly other viruses of the Paramyxoviridae family are present in Paget's disease. However all these data are only suggestive. The viral etiology of Paget's disease cannot be proved until the causative virus is identified and isolated. During the last grant period we were able to transfer virusrelated antigens to susceptible cell lines by co-cultivation and cell fusion. Recently we demonstrated that the putative Paget's disease virus can cause pathology in suckling mouse brain. In this grant application we will use these systems to isolate virus from Paget's disease tissue. Because of the consistent detection of measles virus or respiratory syncytial virus-related antigens we believe that cDNA clones can be obtained using paramyxovirus related antibodies and cDNA probes. We will attempt to identify the putative virus by molecular cloning. If we are successful we can establish a virus in Paget's disease. Should it be proven that Paget's disease is caused by a viral infection, treatment regimens may be developed which utilize either systemic or local administration of anti-viral agents. Vaccines can also be developed. It is conceivable that permanent resolution of the active disease process could result from appropriate therapy. Perhaps immunization at an early age in individuals from families with an apparent genetic predisposition might prevent the disease. Finally knowledge of he pathogenesis of Paget's disease could be applied to the study of other chronic musculoskeletal disorders in which nucleocapsid-like structures have been found. Our short term goals are to confirm or refute the hypothesis that a virus is present in Paget's disease. Our long term goals are to determine if such a virus can cause Paget's disease or be important in the outcome of any of the other chronic musculoskeletal diseases.